PT - JOURNAL ARTICLE AU - Mohammad, Ariz AU - Vanden Broek, Kara AU - Wang, Christopher AU - Daryabeigi, Anahita AU - Jantsch, Verena AU - Hansen, Dave AU - Schedl, Tim TI - Initiation of Meiotic Development Is Controlled by Three Post-transcriptional Pathways in <em>Caenorhabditis elegans</em> AID - 10.1534/genetics.118.300985 DP - 2018 Aug 01 TA - Genetics PG - 1197--1224 VI - 209 IP - 4 4099 - http://www.genetics.org/content/209/4/1197.short 4100 - http://www.genetics.org/content/209/4/1197.full SO - Genetics2018 Aug 01; 209 AB - A major event in germline development is the transition from stem/progenitor cells to entry into meiosis and gametogenesis. This transition requires downregulation of mitotic cell cycle activity and upregulation of processes associated with meiosis. We identify the Caenorhabditis elegans SCFPROM-1 E3 ubiquitin-ligase complex as functioning to downregulate mitotic cell cycle protein levels including cyclin E, WAPL-1, and KNL-2 at meiotic entry and, independently, promoting homologous chromosome pairing as a positive regulator of the CHK-2 kinase. SCFPROM-1 is thus a novel regulator of meiotic entry, coordinating downregulation of mitotic cell cycle proteins and promoting homolog pairing. We further show that SCFPROM-1 functions redundantly, in parallel to the previously described GLD-1 and GLD-2 meiotic entry pathways, downstream of and inhibited by GLP-1 Notch signaling, which specifies the stem cell fate. Accordingly, C. elegans employs three post-transcriptional pathways, SCFPROM-1-mediated protein degradation, GLD-1-mediated translational repression, and GLD-2-mediated translational activation, to control and coordinate the initiation of meiotic development.